The hypothalamus, which is rich in histaminergic neurons, is highly sensiti
ve to aversive stimuli such as stress. Histamine H-3 receptors, which regul
ate histamine release from the presynaptic site, are associated with stress
-induced brain activity. In this study, we investigated the changes of hist
amine content and histamine H-1 and H-3 receptors in the brains of rats sub
jected to stress-induced through food deprivation and physical activity on
a running wheel (food-deprived activity stress). For purposes of comparison
, we also examined the stressful effects of forced swimming on the histamin
ergic neuron system of rats. The H-3 receptor density rapidly declined in t
he acute phase of stress but gradually returned to the control level in the
chronic phase. On the other hand, the H-1 receptor slowly decreased and re
mained at a low level during the chronic phase. These results reveal that t
here is a discrepancy between the levels of H-1 and H-3 receptors in the ac
ute and chronic phases of stress. Brain histamine content gradually increas
ed during the late phase of both food-deprived activity stress and forced s
wimming stress. These changes presumably resulted in the inhibition of hist
aminergic neuronal activity in the chronic stress condition. In accordance
with this hypothesis, the intraventricular administration of histamine sign
ificantly reduced the hyperactivity caused by food-deprived activity stress
. Since extensive exercise and restricted feeding are thought to be associa
ted with anorexia nervosa, the abnormalities in the histaminergic neuron sy
stem might contribute to trait status in anorexia nervosa. (C) 2001 Elsevie
r Science B.V. All rights reserved.